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Optimizing Vascularized Composite Graft Quality Through Ex Vivo Restoration of S-Nitrosothiol Homeostasis After Brain Death
Mohamed Awad, MD, Lin Zhu, MD, PhD, Anand Kumar, MD, James D. Reynolds, PhD.
Case Western Reserve University Department of Plastic & Reconstructive Surgery University Hospitals-Cleveland Medical Center, Cleveland OH
University Hospitals Case Medical Center
2021-02-15
Presenter: Mohamed Awad
Affidavit:
Mohamed Awad
Director Name: Anand Kumar
Author Category: Fellow Plastic Surgery
Presentation Category: Basic Science Research
Abstract Category: General Reconstruction
Background
Current challenges in Vascularized composite allotransplantation (VCA) include mitigating the damage to organs and VCA flaps secondary to brain death (BD). BD appears to impair systemic micro-vascular perfusion by disrupting S-nitrosothiol (SNO) homeostasis, especially S-nitrosohemoglobin (SNO-Hb) the main physiologic regulator of blood flow. We have developed a novel therapeutic drug that can correct these dysfunctions during ex vivo solid organ storage. We hypothesized that same benefits could be realized during composite allograft storage to improve the quality of the transplanted tissue.
Methods
Vascularized composites tissue was obtained from swine, after induction of BD. Each composite was then prepped and placed in a solid organ hypothermic active storage system; flow and resistance measures were recorded during storage. Control flaps were perfused with a standard organ preservation solution while the experimental group received solution that was aerated with the S-nitroylsating agent ethyl nitrite (ENO). flow rate and resistance were recorded during the storage period; tissue hypoxia was also quantified before and after active perfusion.
Results
BD produced a significant decline in circulating SNO-Hb levels. Addition of ENO increased flap flow and decreased resistance; these benefits were more pronounced in the abdominal blocks. Post ENO-treated flaps had lower levels of inducible NO synthase and the hypoxia marker Hif1 protein and higher levels of the anti-apoptotic protein BcL2, all suggestive of an enhancement of tissue oxygenation.
Conclusion
Nitrosylation therapy to maintain endocrine nitric oxide bioactivity reduces flap stress and may improve the quality of composite tissue grafts prior to transplantation.
